Cited by 231Muscle Physiology and DisordersSpaceflight effects on biologyNutrition and Health in Aging

Age-related differences in apoptosis with disuse atrophy in soleus muscle

Leeuwenburgh, Christiaan, Gurley, Cathy M., Strotman, Beau A., Dupont-Versteegden, Esther E.·2005·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

Abstract

Muscle atrophy is associated with a loss of muscle fiber nuclei, most likely through apoptosis. We investigated age-related differences in the extent of apoptosis in soleus muscle of young (6 mo) and old (32 mo) male Fischer 344 x Brown Norway rats subjected to acute disuse atrophy induced by 14 days of hindlimb suspension (HS). HS-induced atrophy (reduction in muscle weight and cross-sectional area) was associated with loss of myofiber nuclei in soleus muscle of young, but not old, rats. This resulted in a significant decrease in the myonuclear domain (cross-sectional area per nucleus) in young and old rats, with changes being more pronounced in old animals. Levels of apoptosis (TdT-mediated dUTP nick end labeling and DNA fragmentation) were higher in soleus muscles of old control rats than young animals. Levels were significantly increased with HS in young and old rats, with the greatest changes in old animals. Caspase-3 activity in soleus muscle tended to be increased with age, but changes were not statistically significant (P=0.052). However, with HS, caspase-3 activity significantly increased in young, but not old, rats. Immunohistochemistry showed that the proapoptotic endonuclease G (EndoG, a mitochondrion-specific nuclease) was localized in the subsarcolemmal mitochondria in control muscles, and translocation to the nucleus occurred in old, but not young, control animals. There was no difference between EndoG total protein content in young and old control rats, but EndoG increased almost fivefold in soleus muscle of old, but not young, rats after HS. These results show that deregulation of myonuclear number occurs in old skeletal muscle and that the pathways involved in apoptosis are distinct in young and old muscles. Apoptosis in skeletal muscle is partly mediated by the subsarcolemmal mitochondria through EndoG translocation to the nucleus in response to HS.

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Crossref · 10.1152/ajpregu.00576.2004

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  • Aged skeletal muscles display increased mitochondrial-mediated apoptosis.

    “Notably, aged skeletal muscles display impaired mitochondrial energetics (Trounce et al. 1989; Short et al. 2005; Gouspillou et al. 2010; Lanza et al. 2012; Gouspillou et al. 2014a) and increased mitochondrial‐mediated apoptosis (Selman et al. 2003; Dirks & Leeuwenburgh, 2004; Leeuwenburgh et al. 2005; Chabi et al. 2008; Marzetti et al. 2008; Picard et al. 2010; Picard et al. 2011; Gouspillou et a”

    From Parkin overexpression protects from ageing‐related loss of muscle mass and strength (2019) · cites this paper as Leeuwenburgh et al. 2005

  • Apoptosis increases with ageing and contributes to sarcopenia.

    “Apoptosis is well known to increase with ageing and contribute to sarcopenia (Dirks & Leeuwenburgh, 2004; Leeuwenburgh et al. 2005; Chabi et al. 2008; Gouspillou et al. 2014b).”

    From Parkin overexpression protects from ageing‐related loss of muscle mass and strength (2019) · cites this paper as Leeuwenburgh et al. 2005

  • Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents and humans.

    “Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents (4, 7, 26, 34, 47, 77, 88, 130), and humans (44, 145).”

    From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [77]

  • Aging rat soleus muscle showed translocation of Endonuclease G from the mitochondria to the nucleus suggesting a caspase-independent process.

    “In contrast, aging rat soleus muscle showed translocation of Endonuclease G from the mitochondria to the nucleus suggesting a caspase-independent process (Leeuwenburgh et al., 2005).”

    From Programmed cell death in aging (2015) · cites this paper as Leeuwenburgh et al., 2005

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Authors
Leeuwenburgh, C., Gurley, C. M., Strotman, B. A., & Dupont-Versteegden, E. E.
Affiliations
University of Florida (US)
Venue
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Published
2005-05
Volume
288
Issue
5
Pages
R1288-R1296
ISSN
  • 0363-6119 (ISSN-L)
  • 1522-1490
OpenAlex
W2045709794
Cited by
231
References
70
Citations by year
2026: 1 · 2025: 9 · 2024: 16 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 9 · 2017: 5 · 2016: 11 · 2015: 14 · 2014: 7 · 2013: 8 · 2012: 13
FWCI
6.78
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r03ag020407-01)
  • National Institute on Aging (AG-20407, AG-21042, R01AG021042)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR47577, R01AR047577)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
muscle atrophy, disuse atrophy, apoptosis, soleus muscle, aging, hindlimb unloading, myonuclear domain, caspase-3, endonuclease G, mitochondrial translocation, subsarcolemmal mitochondria, DNA fragmentation, skeletal muscle
MeSH terms
Aging, Animals, Endodeoxyribonucleases, Hindlimb, Male, Muscular Atrophy, Rats, Inbred BN, Rats, Inbred F344, Apoptosis, Muscle, Skeletal, Caspases, Rats, Caspase 3

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